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C. A. Curcio, M. Rudolf, M. F. Chimento, M. E. Clark, C.-M. Li, N. E. Medeiros; A Morphological Comparison of Macular and Extra-Macular Drusen From Eyes With Early Age-Related Maculopathy (ARM). Invest. Ophthalmol. Vis. Sci. 2007;48(13):3015.
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to determine if macular and extra-macular drusen have differences in fine structure that could underlie differences in histological fragility, ex vivo autofluorescence, and association with risk for choroidal neovascularization.
Eyes were preserved within 6 hr postmortem (in buffered paraformaldehyde with or without glutaraldehyde). Drusen were isolated manually from 9 eyes of 7 donors (age, 69-102 yr) with grossly visible early ARM. Pellets containing macular or extra-macular drusen were post-fixed in osmium-paraphenylenediamine to accentuate neutral lipid, embedded in epoxy resin, and sectioned for evaluation by light microscopy (LM) and transmission electron microscopy (TEM).
Extra-macular drusen, appearing cloudy or transparent*, were resilient when isolated. Macular drusen, appearing liquefied, semi- crystallized, or crystalline, were friable when isolated. To date we examined 303 drusen by LM and subjected these observations to contingency analysis (111 from macula, 192 from extra-macula; 7 eyes of 6 donors). Relative to extra-macular regions, the macula had a significantly 1) higher proportion of drusen enveloped by basal laminar deposit, 2) smaller proportion of drusen with completely intact contents, 3) smaller proportion of drusen with homogenous contents, 4) smaller proportion of drusen with intensely OTAP-stained contents, 5) smaller proportion of drusen with interior substructures* such as cores, shells, or invading cells, 6) smaller proportion of drusen with electron-lucent inclusions, and 7) a higher proportion of drusen with partially or totally calcified contents. By TEM (in progress), macular drusen appear more loosely packed, containing an electron-dense membrane-like material not apparent in extra-macular drusen.
Extra-macular drusen are far more abundant than macular drusen, making them more tractable for study, but whether they are indeed acceptable surrogates is unresolved. These data, generated from drusen identically handled from two regions of the same eyes, suggest that macular drusen are collectively more fragile and show less evidence of the dynamic processes inferred from detailed study of extra-macular drusen. Because basal linear deposit is thought to resemble drusenoid material distributed diffusely rather than focally, it is possible that our results will be applicable to this specific, insidious, but elusive ARM lesion. *Li et al., 2006 IOVS 47:3119
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